Clinical Outcomes with Repeated Administration of Budesonide/Formoterol in Asthma

7 Apr, 22

Introduction

The risk of severe exacerbations is reduced with budesonide-formoterol reliever compared to short-acting ?2 agonist (SABA) reliever in mild asthma. However, the bronchodilator and anti-inflammatory effects of the repeated administration of budesonide/formoterol compared to SABA is not clear.

Aim

This study compares the bronchodilator effects of repeated administration of budesonide/formoterol 200/6?µg to 200 µg salbutamol in adults with stable asthma and moderate to severe airflow obstruction.

Method

Study Design

Open-label, cross-over, single-center randomized controlled trial.

Patient Profile

Asthmatic adults aged between 16 to 65 years
Forced expiratory volume in 1 sec (FEV1) 40-70% predicted
Bronchodilator reversibility with FEV1 >12% and >200 ml

Treatment Strategy

The eligible patients were randomized into 2 groups using the following regimen:
- Salbutamol regimen – salbutamol 200?µg 2 actuations via metered dose inhaler (MDI) at t=0, 30, 60, 90?min, followed by salbutamol 2.5?mg via nebulizer at t=120, 140, 160 and 420?min
- Budesonide/formoterol regimen – budesonide/formoterol 200/6?µg one actuation at t=0, 30, 60, 90?min, followed by two actuations at t=120, 140, 160 and 420?min.
- Secondary outcomes included repeat measures of FEV₁, serum potassium, heart rate, and adverse events.

End Points

Primary Endpoints

FEV₁ after 180?min

Secondary Endpoints

FEV₁at different timepoints
Fractional exhaled nitric oxide (FeNO)
Serum potassium
Blood eosinophil count
Heart rate
Adverse events (AEs).

Results

All the recruited 39 patients were included in the intention-to-treat analysis.
The baseline characteristics of the cohort were as below
- Mean age 46 years
- FEV₁% predicted 60.7
- Fractional exhaled nitric oxide (FeNO) 44.6
Two patients withdrew due to AEs (QT_CF prolongation and T wave abnormalities) after the first intervention with salbutamol.
The mean change from baseline FEV₁ 180?min after randomization for salbutamol and budesonide/formoterol regimens was 0.71 L, and 0.58 L, respectively; with a mean (SD) paired difference of −0.10 (0.40) L, N=37, and a model-based estimated difference (95% CI) −0.12 (−0.25 to 0.02) L, p=0.088.
Salbutamol resulted in significantly greater FEV₁ from 30 to 240?min, but lesser FEV₁ at 360 and 420?min.
When averaged over all the tome points, the salbutamol group had lower FeNO as compared to the budesonide/formoterol group; p<0.001.
The serum potassium level was significantly lower in the salbutamol group; p<0.001.
The blood eosinophil count was higher in the budesonide/formoterol group after 180 mins but not after 480 min.
The heart rate was lower in the patients following the budesonide/formoterol regimen.
There were significantly higher AEs in the salbutamol group; p<0.001.

Conclusions

The comparative bronchodilator effects of repeated administration of salbutamol 200?µg and budesonide/formoterol 200/6?µg differed depending on the time of measurement in patients with asthma.
Administration of salbutamol was associated with greater cardiovascular effects and more adverse events.

Eur Respir J. 2022 Feb 3;2102309. Doi: 10.1183/13993003.02309-2021.